# Acral melanoma

Source: https://onco.cc/cancers/acral-melanoma/  
OnCo record `acral-melanoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Acral melanoma grows on the soles, palms or under a nail, places without sun exposure, and it is the commonest melanoma in people with darker skin. It is often mistaken for a wart, bruise or fungal nail and so found late; treatment follows skin melanoma, but immunotherapy works less often because the tumour carries fewer mutations.

## Summary

Acral melanoma arises on the glabrous skin of the palms, soles and nail apparatus and is not caused by ultraviolet light; its genome has few point mutations but frequent amplifications of CCND1, CDK4 and TERT and other structural changes. BRAF V600 mutations occur in about one in six tumours, NRAS in a similar share and KIT alterations in around one in ten. Delay in diagnosis is the rule, since lesions are mistaken for warts, calluses, haematomas or fungal nail infection, and thick, ulcerated primaries with nodal spread are common at presentation; stage for stage, outcomes are somewhat worse than for other cutaneous melanomas.

Management follows cutaneous melanoma: excision with margins set by thickness, which for digits may mean amputation of the distal phalanx, sentinel node biopsy for primaries over 0.8 millimetres, and adjuvant anti-PD-1 antibody or, for BRAF-mutant disease, dabrafenib-trametinib after resection of stage III disease. Reconstruction of weight-bearing soles is a particular surgical problem. No adjuvant or advanced-disease trial has been run in acral melanoma alone; the evidence is extrapolated from trials in which acral tumours were a small minority.

Response to PD-1 blockade is lower than in melanoma of sun-damaged skin: a Japanese multicentre series of 193 patients found responses in 17 percent, and a United States series found responses in about a third. Combination immunotherapy is preferred where tolerated. Imatinib produces responses in roughly a quarter of KIT-mutant tumours, tunlametinib is approved in China for NRAS-mutant melanoma, and CDK4/6 inhibitors are being tested against the CDK4 pathway amplifications that characterise the subtype.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Acral lentiginous melanoma; Melanoma of the palms, soles and nail beds; Subungual melanoma
- Tags: subtype-page
- Group: skin
- Burden: Acral melanoma arises on the palms, soles and under the nails; its absolute incidence is similar in every population, so it is a small minority of melanomas in people with fair skin but the commonest melanoma subtype in people of African and Asian ancestry, accounting for about four in ten melanomas in China.
- Subtypes: Acral lentiginous melanoma of the sole (commonest site); Subungual melanoma (nail apparatus, often with Hutchinson sign); Palmar melanoma; KIT-mutant acral melanoma (imatinib candidates); BRAF V600-mutant acral melanoma (targeted therapy eligible); CDK4 pathway-amplified acral melanoma (CDK4/6 inhibitor trials)
- Biomarkers: Breslow thickness and ulceration; BRAF V600 mutation; NRAS mutation; KIT mutation or amplification; CCND1, CDK4 and TERT amplification (research); Low tumour mutational burden

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/acral-melanoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/acral-melanoma/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/acral-melanoma/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/acral-melanoma/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/acral-melanoma/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/acral-melanoma/#evidence [4 trials, 6 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/acral-melanoma/#science [6 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/acral-melanoma/where-you-are/ [10 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/acral-melanoma/#living-with-it [16 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/acral-melanoma/coming/ [8 medicines, 1 trial, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/acral-melanoma/data/ [43 connected records]

## Standard of care

- Diagnosis: Dermoscopy of the parallel ridge pattern and biopsy of any changing pigmented lesion of the palm, sole or nail; nail matrix biopsy for longitudinal melanonychia with Hutchinson sign. ([Dermoscopy, total-body photography & AI skin analysis](https://onco.cc/technologies/dermoscopy-ai/), [Skin cancer screening (visual skin examination)](https://onco.cc/technologies/skin-cancer-screening/))
- Localised disease: Wide local excision with thickness-based margins, distal amputation for subungual disease when needed, sentinel lymph node biopsy for primaries over 0.8 mm. ([Wide local excision](https://onco.cc/terms/wide-local-excision/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Breslow thickness](https://onco.cc/terms/breslow-thickness/))
- Resected stage III: Adjuvant nivolumab or pembrolizumab; dabrafenib-trametinib for BRAF V600-mutant disease; neoadjuvant immunotherapy for macroscopic nodes as in NADINA. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [NADINA](https://onco.cc/trials/nadina/))
- Advanced disease: Nivolumab plus ipilimumab or anti-PD-1 monotherapy; BRAF-MEK inhibitors for BRAF-mutant tumours; imatinib for KIT-mutant tumours; tunlametinib for NRAS-mutant disease in China; trials of CDK4/6 inhibitors. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Tunlametinib](https://onco.cc/drugs/tunlametinib/), [Palbociclib](https://onco.cc/drugs/palbociclib/))

## State of the art

- Treatment is extrapolated from cutaneous melanoma trials in which acral tumours were a small minority.
- Response rates to PD-1 blockade are lower and the subtype's amplification-driven biology has no approved drug yet.
- Chinese and Japanese cohorts, where the subtype is common, now supply most of the evidence.

## Open problems

- Late diagnosis remains the main cause of poor outcomes and awareness in people with darker skin is low.
- No trial has been designed for acral melanoma alone outside East Asia.
- The amplification-driven genome offers targets (CDK4, CCND1) without a proven drug.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acral_lentiginous_melanoma
- Anti-PD-1 in 193 Japanese patients with acral melanoma (Annals of Oncology 2020): https://doi.org/10.1016/j.annonc.2020.05.031
- Wikipedia: https://en.wikipedia.org/wiki/Acral_lentiginous_melanoma

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Conjunctival melanoma](https://onco.cc/cancers/conjunctival-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Mucosal melanoma](https://onco.cc/cancers/mucosal-melanoma/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/), [Uveal melanoma](https://onco.cc/cancers/uveal-melanoma/)
- technologies: [Dermoscopy, total-body photography & AI skin analysis](https://onco.cc/technologies/dermoscopy-ai/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/), [Skin cancer screening (visual skin examination)](https://onco.cc/technologies/skin-cancer-screening/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/), [KIT](https://onco.cc/targets/kit/), [MEK1/2](https://onco.cc/targets/mek/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Lifileucel](https://onco.cc/drugs/lifileucel/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Palbociclib](https://onco.cc/drugs/palbociclib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Tunlametinib](https://onco.cc/drugs/tunlametinib/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Breslow thickness](https://onco.cc/terms/breslow-thickness/), [SF3B1 mutation](https://onco.cc/terms/sf3b1-mutation/), [Ulceration (melanoma)](https://onco.cc/terms/ulceration-melanoma/), [Wide local excision](https://onco.cc/terms/wide-local-excision/)
- key papers: [Anti-PD-1 checkpoint inhibitor therapy in acral melanoma: a multicentre study of 193 Japanese patients](https://onco.cc/key-papers/paper-nakamura-anti-pd1-acral-melanoma-ann-oncol-2020/), [Distinct sets of genetic alterations in melanoma](https://onco.cc/key-papers/paper-curtin-melanoma-genetic-alterations-nejm-2005/), [Imatinib for melanomas harbouring mutationally activated or amplified KIT arising on mucosal, acral and chronically sun-damaged skin](https://onco.cc/key-papers/paper-hodi-imatinib-kit-melanoma-jco-2013/), [NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma](https://onco.cc/key-papers/paper-nadina-nejm-2024/), [Somatic activation of KIT in distinct subtypes of melanoma](https://onco.cc/key-papers/paper-curtin-kit-melanoma-jco-2006/), [Whole-genome landscapes of major melanoma subtypes](https://onco.cc/key-papers/paper-hayward-melanoma-whole-genome-nature-2017/)
- trials: [A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)](https://onco.cc/trials/seacraft-2/), [A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastat](https://onco.cc/trials/nct06797297/), [Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma](https://onco.cc/trials/nct06008106/), [NADINA](https://onco.cc/trials/nadina/)

---
JSON: https://onco.cc/api/v1/entities/acral-melanoma.json